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Intraoperative radiolymphoscintigraphy improves sentinel lymph node identification for patients with melanoma

BACKGROUND The sentinel lymph node (SLN), the first node draining the primary tumor site, has been shown to reflect the histologic features of the remainder of the lymphatic basin in patients with melanoma. Intraoperative localization of the SLN, first proposed by Morton and colleagues, has been accomplished with the use of a vital blue dye mapping technique. Technical difficulties resulting in unsuccessful explorations have occurred in up to 20% of the dissections. OBJECTIVES The authors aimed to define the SLN using gamma detection probe mapping and to determine whether intraoperative radiolymphoscintigraphy using technetium sulfur colloid and a hand-held gamma-detecting probe could be used to improve detection of all SLNs for patients with melanoma. METHODS To ensure that all initial nodes draining the primary site were removed at the time of selective lymphadenectomy, the authors used intraoperative radiolymphoscintigraphy to confirm the location of the SLN, which was determined initially with the preoperative lymphoscintigram and the intraoperative vital blue dye injection. PATIENT POPULATION The patient population consisted of 106 consecutive patients who presented with cutaneous melanomas larger than 0.75 mm in all primary site locations. RESULTS The preoperative lymphoscintigram revealed that 22 patients had more than one lymphatic basin sampled. Two hundred SLNs and 142 neighboring non-SLNs were harvested from 129 basins in 106 patients. After the skin incision was made, the mean ratio of hot spot to background activity was 8.5:1. The mean ratio of ex vivo SLN-to-non-SLN activity for 72 patients who had SLNs harvested was 135.6:1. When correlated with the vital blue dye mapping, 139 of 200 (69.5%) SLNs demonstrated blue dye staining, whereas 167 of 200 (83.5%) SLNs were hot according to radioisotope localization. With the use of both intraoperative mapping techniques, identification of the SLN was possible for 124 of the 129 (96%) basins sampled. Micrometastases were identified in SLNs of 16 of the 106 (15%) patients by routine histologic analysis. CONCLUSION The use of intraoperative radiolymphoscintigraphy can improve the identification of all SLNs during selective lymphadenectomy.

Phase I/II trial for the treatment of cutaneous and subcutaneous tumors using electrochemotherapy

Electroporation is a process that causes a transient increase in the permeability of cell membranes. It can be used to increase the intracellular concentration of chemotherapeutic agents in tumor cells (electrochemotherapy; ECT). A clinical study was initiated to determine if this mode of treatment would be effective against certain primary and metastatic cutaneous malignancies. A group of six patients, three with malignant melanoma, two with basal cell carcinoma, and one with metastatic adenocarcinoma, were enrolled in the study. The treatment was administered in a two‐step process.

Results of complete lymph node dissection in 83 melanoma patients with positive sentinel nodes.

AbstractBackground: The technique of sentinel lymph node (SLN) biopsy for melanoma provides accurate staging information because the histology of the SLN reflects the histology of the entire basin, particularly when the SLN is negative. Methods: We combined two mapping techniques, one using vital blue dye and the other using radiolymphoscintigraphy with a hand-held gamma Neoprobe, to identify the SLN in 600 consecutive patients with stage I–II melanoma. The SLNs were examined using conventional histopathology and immunohistochemistry for S-100. Results: Eighty-three (13.9%) patients had micrometastatic disease in the SLNs. Thirty percent of patients with primary melanomas greater than 4.0 mm in thickness had positive SLNs, followed by 48 of 267 (18%) of patients with tumors between 1.5 mm and 4 mm, and 12 of 169 (7%) of those with lesions between 1.0 mm and 1.5 mm. No patient with a tumor less than 0.76 mm in thickness had a positive SLN. Sixty-four of the 83 SLN-positive patients consented to undergo complete lymph node dissection (CLND), and five of 64 (7.8%) of the CLNDs were positive. All patients with positive CLNDs had tumor thicknesses greater than 3.0 mm. Conclusions: The rate of SLN-positive patients increases with increasing thickness of the melanoma. SLN-positive patients with primary lesions less than 1.5 mm in thickness may have disease confined to the SLN, thus rendering higher-level nodes free of disease, and may not require a CLND.

The Use of Intraoperative Radiolymphoscintigraphy for Sentinel Node Biopsy in Patients with Malignant Melanoma

background Selective lymphadenectomy or “sentinel node” biopsy Ms been introduced recently by Morton and colleagues (Arch Surg 1992;127:392–9) to stage patients with intermediate and thick malignant melanomas. It has proven to be an effective way to identify nodal basins at risk for metastasis without the morbidity of a complete lymph node dissection. The majority of biopsies can be performed under local anesthesia with small incisions, but technical difficulties occasionally result in unsuccessful explorations. Identification of the sentinel node can be enhanced by a intraoperative radiolymphoscintigraphy, a technique introduced Alex and Krag (Surg Oncol 1993;137–43) tint uses radiolabeled sulfur colloid and a hand‐held gamma probe. objective We used intraoperative radiolymphoscintigraphy in conjunction with 1% lymphazurin blue dye to define the sentinel node(s) in 148 patients with greater than 0.76 mm in thickness or Clark level TV melanomas. Sentinel lymph nodes were isolated, harvested, and examined using conventional histopathology, and immunohistochemistry for S‐100 and HMB‐45 antibodies. results The overall success rate of sentinel lymph node localization was 97% using a combination of the two techniques. Twenty‐one (34%) patients had micrometastasis, and 17 of these subsequently underwent complete lymph node dissection. A total of 220 of 275 (80%) sentinel nodes harvested were radioactive or “hot” compared with 165 of 275 (60%) with the blue dye alone. Four of the patients with micrometastasis had sentinel nodes positive by gamma probe, but negative by blue dye mapping techniques. conclusion Our results suggest that intraoperative radiolymphosintigraphy using a hand‐held gamma detecting probe improves the identification of sentinel lymph nodes during selective lymphadenectomy. This may reduce the number of “unsuccessful explorations” using the vital blue dye technique for lymphatic mapping, and appeal to a greater variety of surgeons, including dermatologic surgeons.

Multiple primary melanomas: Implications for screening and follow-up programs for melanoma

AbstractBackground: Once individuals are diagnosed with malignant melanoma, they are at an increased risk of developing another melanoma when compared with the normal population. Methods: To determine the impact of an intensive follow-up protocol on the stage of disease at diagnosis of subsequent primary melanomas, a retrospective query was performed of an electronic medical record database of 2,600 consecutively registered melanoma patients. Results: Sixty-seven patients (2.6%) had another melanoma diagnosed at the time of presentation to the clinic or within 2 months (synchronous) and another 44 patients (1.7%) developed a second primary melanoma during the follow-up period (metachronous). For the 44 patients diagnosed with metachronous lesions, the Breslow mean tumor thickness for the first invasive melanoma was 2.27 mm compared with 0.90 mm for the second melanoma. The first melanomas diagnosed are thicker by an average of 3.8 mm (p=0.008). The mean Clark level for the initial melanoma was greater than the mean level for subsequently diagnosed melanomas (p=0.002). Twenty-three percent of the initial melanomas were ulcerated, whereas only one of the second primary lesions showed this adverse prognostic factor (p=0.002). Conclusions: Once individuals are diagnosed with melanoma, they are in a high-risk population for having other primary site melanomas diagnosed and should be placed in an intensive follow-up protocol consisting of a complete skin examination.

Evaluation of new putative tumor markers for melanoma

AbstractBackground: The early diagnosis of recurrent melanoma can contribute to better outcome if the disease can be surgically resected or if the metastases are responsive to systemic therapies. Lipid-associated sialic acid (LASA-P) and the S-100 protein (S-100) were evaluated as tumor markers for melanoma with the goal of early detection of recurrence. Methods: Sixty-seven patients were identified who had levels of S-100 and LASA-P drawn during their clinical course. A multivariate regression analysis was performed to determine the significance of the serum markers in relation to other prognostic factors for melanoma. Results: After a median follow-up of 30 months, 58 patients had recurrences, and 49 patients died of disease. LASA-P elevation was not associated with the time to recurrence (p=0.2176) or survival (p=0.2507). S-100 positivity was a significant predictor of recurrence (p<0.0001) and survival (p=0.0059). The median time to recurrence for S-100-positive and S-100-negative patients was 7.6 and 33.8 months, respectively. The median survival time was 59.2 months for S-100-negative patients and 29.6 months for patients positive for S-100. Conclusions: Serum S-100 shows significant correlations to both time to recurrence and survival and could be useful in the clinical detection of malignant melanoma.

Accurate Nodal Staging of Malignant Melanoma.

The incidence of malignant melanoma is increasing at a faster pace than that of any other cancer in the United States. It is estimated that people born in the year 2000 will have a 1:75 risk of developing melanoma sometime during his or her lifetime. Stimulated by novel lymphatic mapping techniques, the surgical care of the melanoma patient is evolving toward more conservative resections that can provide the same staging information but without the added morbidity of more radical surgeries. This approach promises to yield positive results in the age of health care reform, outcome measurements, and cost:benefit considerations.

The Role of Selective Lymphadenectomy in the Management of Patients with Malignant Melanoma

background A novel surgical technique based on selective lymphadenectomy was used to stage 132 patients with intermediate and thick cutaneous malignant melanoma. Preoperative and intraoperative lymph node mapping techniques were used to ascertain regional lymph node basins at risk for metastasis, and to identify the first node(s) the afferent lymphatics encounter in the basin, defined as the “sentinel” node(s). It has been shown that the histology of the sentinel node reflects the histology of the rest of the nodal basin, and according to preliminary studies using this technique, the likelihood of bypassing the sentinel node(s) to “higher” level nodes is less than 2%. Epidemiologic studies indicate that the long‐term survival of patients with melanomas of intermediate thickness or greater is significantly compromised if regional lymph nodes are involved. Yet, the utility of performing lymph node dissections for the purposes of staging only is controversial, not only because of the morbidity and expense of the procedure, but the lack of proven survival benefit. objective In the present study, we performed preoperative and intraoperative lymphatic mapping, harvested clinically normal sentinel nodes, and examined them for micrometastasis by light microscopy. Both conventional stains and immunocytochemistry for S‐100 protein and HMB‐45 antibodies were performed, and only those patients with documented micrometastasis received complete lymph node dissections. results The sentinel node(s) was identified in each of the patients. Micrometastasis disease was detected in 31 (23%) of the patients by selective lymphadenectomy, and the sentinel node(s) was the only node involved in 83% of the cases upon subsequent complete nodal dissection. conclusion Our preliminary results suggest that selective lymphadenectomy following lymphatic mapping is an effective procedure for staging melanoma patients with lesions of intermediate thickness or greater. Our results indicate that sentinel lymph nodes may be successfully identified and harvested in the majority of patients, and that they may be examined for the first evidence of micrometastasis without the need of a complete nodal dissection. Information as to whether micrometastases are present in the sentinel node would be valuable in staging patients, and identifying candidates for complete nodal dissections. We are participating in a National Cancer Institute‐sponsored multicenter trial to ascertain whether this surgical approach can impact on the recurrence rate and survival of patients with stage 1 and 2 melanoma.

Efficacy of hyperthermic isolated limb perfusion for extremity-confined recurrent melanoma

AbstractBackground: Recurrent melanoma of the extremity has been treated by local excision, systemic chemotherapy, amputation, or a combination of these approaches. Hyperthermic isolated limb perfusion (HILP) provides a method of limb preservation through isolation, allowing the administration of chemotherapy in higher doses than is possible through systemic treatment. Methods: An experimental group of 59 HILP patients with melanoma recurrences of the extremity was studied prospectively. A control group of 248 melanoma patients with similar recurrences was excluded from HILP because their recurrences were in non-extremity locations. The experimental group underwent HILP and excision; the control group had excision only. The experimental procedure consisted of vascular isolation of the affected extremity and a 1-hour perfusion with melphalan. Temperatures were maintained at 40°C in the perfusion circuit. Results: The HILP patients had a lower rate of locoregional recurrence (P=.028) and demonstrated increased survival (P=.026) compared to the control group. In multivariate regression analysis, which included age, ulceration and thickness of the primary, and the treatment variable of perfusion, age (P=.02) and perfusion for the treatment of recurrence (P=.006) were significant predictors of survival. Conclusions: HILP improves prognosis by sterilizing the treated extremity, controlling locoregional disease, and perhaps preventing metastasis, thus having a positive impact on overall survival.